With the introduction of metrizamide, the first commercially available non-ionic contrast medium, many of the serious reactions associated with water-soluble, ionic agents have been eliminated. However, minor adverse reactions are still commonly encountered with metrizamide and a few major reactions have also occurred. To study the effects on the central nervous system (CNS) of non-ionic contrast media, we will perform a series of experiments with metrizamide and iohexol in an attempt to grade their toxicity and explain why these side effects occur, how they might be aggravated by various circumstances and how these risks might be decreased. We propose to do this by studying the penetration and localization of these two contrast media in the CNS since we believe penetration, which depends on the concentration of the contrast medium in the cerebrospinal fluid (CSF) and the time it is in contact with nervous tissue, is the basis of toxicity. We also propose to study the possible interference of metrizamide with the glucose metabolism of the CNS, and the stability of metrizamide in vivo as well as in vitro. We plan to study means of decreasing penetration of metrizamide into the CNS, and ways of avoiding interference in glucose metabolism as well as comparative behavior of iohexol and metrizamide. The major goals of the proposed work are: 1) a better understanding of the drainage of contrast media from the subarachnoid space, 2) an evaluation of degree of penetrance into the CNS, for both metrizamide and iohexol, under "normal" circumstances and after changing the rate of production of CSF, 3) a better understanding of the mechanism by which metrizamide produces side effects, which could help in designing of less toxic contrast media 4) an evaluation and comparison of toxicity of metrizamide and iohexol, as measured by disturbance in neuronal metabolism. A better understanding of the mechanism and factors influencing contrast media toxicity will allow us to contribute to decreasing side effects in future examinations of the subarachnoid space.